NDLI: Pancreatic progenitor-derived hepatocytes are viable and functional in a 3D high density bioreactor culture system

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Pancreatic progenitor-derived hepatocytes are viable and functional in a 3D high density bioreactor culture system

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Toxicology Research Vol -4

Toxicology Research Vol -3

Toxicology Research Vol -2

Toxicology Research Vol -1

Pancreatic progenitor-derived hepatocytes are viable and functional in a 3D high density bioreactor culture system

Content Provider	Royal Society of Chemistry (RSC)
Author	Stroux, A. Wright, M. C. Zeilinger, K. Knöspel, F. Richter, M. Tröbs, S. Probert, P. M. E. Fairhall, E. A. Hoffmann, S. A. Oakley, F.
Copyright Year	2016
Abstract	The rat pancreatic progenitor cell line B-13 is of interest for research on drug metabolism and toxicity since the cells trans-differentiate into functional hepatocyte-like cells (B-13/H) when treated with glucocorticoids. In this study we investigated the trans-differentiation and liver-specific functions of B-13/H cells in a three-dimensional (3D) multi-compartment bioreactor, which has already been successfully used for primary liver cell culture. Undifferentiated B-13 cells were inoculated into the bioreactor system and exposed to dexamethasone to promote hepatic trans-differentiation (B-13/HT). In a second approach, pre-differentiated B-13 cells were cultured in bioreactors for 15 days to evaluate the maintenance of liver-typical functions (B-13/HP). During trans-differentiation of B-13 cells into hepatocyte-like cells in the 3D bioreactor system (approach B-13/HT), an increase in glucose metabolism and in liver-specific functions (urea and albumin synthesis; cytochrome P450 [CYP] enzyme activity) was observed, whereas amylase – characteristic for exocrine pancreas and undifferentiated B-13 cells – decreased over time. In bioreactors with pre-differentiated cells (approach B-13/HP), the above liver-specific functions were maintained over the whole culture period. Results were confirmed by gene expression and protein analysis showing increased expression of carbamoyl-phosphate synthase 1 (CPS-1), albumin, CYP2E1, CYP2C11 and CYP3A1 with simultaneous loss of amylase. Immunohistochemical studies showed the formation of 3D structures with expression of liver-specific markers, including albumin, cytokeratin (CK) 18, CCAAT/enhancer-binding protein beta (CEBP-β), CYP2E1 and multidrug resistance protein 2 (MRP2). In conclusion, successful culture and trans-differentiation of B-13 cells in the 3D bioreactor was demonstrated. The requirement for only one hormone and simple culture conditions to generate liver-like cells makes this cell type useful for in vitro research using 3D high-density culture systems.
Starting Page	278
Ending Page	290
Page Count	13
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	5
Issue Number	1
Journal	Toxicology Research
DOI	10.1039/c5tx00187k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Hormone Cell culture Cytokeratin Dexamethasone Amylase Enzyme Liver Hewlett-Packard Cytochrome P450 Albumin Glucose Metabolism CP System Protein Three-dimensional space Urea Bioreactor Gene CYP2E1 Pancreas Progenitor cell Multiple drug resistance
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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Presence of cytochrome p450 enzymes in human cd34+ haematopoietic progenitor cells.

In vitro induction of cytochrome p450 enzymes in hepatocytes isolated.

Utility of B-13 Progenitor-Derived Hepatocytes in Hepatotoxicity and Genotoxicity Studies

Inhibition of Human Cytochrome P450 3A4 by Cholesterol

Plateable cryopreserved human hepatocytes for the assessment of cytochrome P450 inducibility: experimental condition-related variables affecting their response to inducers.

© Copr. 1949-1998 Hewlett-Packard Co.HEWLETT-PACKARD JOURNAL Technical Information from the Laboratories of Hewlett-Packard Company

Substrate stiffness regulates primary hepatocyte functions

A novel 3D liver organoid system for elucidation of hepatic glucose metabolism

Toxicological implications of mitochondrial localization of CYP2E1

Pancreatic progenitor-derived hepatocytes are viable and functional in a 3D high density bioreactor culture system

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